M11 - ASSESSING THE ROLE OF LONG NONCODING RNAS (LNCRNAS) IN AUTISM SPECTRUM DISORDERS

Abstract

Background The contribution of non-coding genomic elements remains largely unexplored in Autism Spectrum Disorders (ASD). Long non-coding RNAs (lncRNAs) are increasingly recognized for their role in transcription regulation, and likely contribute to transcriptome dysregulation in ASD. Methods We are applying a combination of short-read and long-read RNA-Seq, with and without lncRNA capture to unveil the role of lncRNAs in ASD. As lncRNAs are poorly represented in standard RNA-Seq experiments, we used capture RNA-Seq (Capture-Seq) to quantify lncRNA expression in postmortem prefrontal cortex and cerebellum tissues in a cohort of 40 ASD and controls. We additionally combined full-length (PacBio) isoform sequencing (Iso-Seq) with capture (Capture-IsoSeq) to build a comprehensive map of brain-expressed lncRNAs. Results The enrichment by Capture-Seq increased the lncRNA fraction of our RNA-Seq datasets from 5% to 57%. We identified 28 differentially expressed (false discovery rate (FDR) Discussion Our Capture enriched sequencing approaches substantially improved our ability to profile lncRNA expression and reconstruct poorly annotated lncRNA isoforms. We have identified many DE lncRNA/TUCP transcripts in a cohort of 40 ASD and controls from two different brain regions as a key step towards understanding the role of lncRNAs in ASD etiology.